#3412 the thrombotic events in patients with anca-associated vasculitis: a retrospective cohort study and mendelian randomization analysis

Abstract Background and Aims Thrombotic event in ANCA-associated vasculitis (AAV) was prevalent but not clarified in the causal relationship between AAV and thrombotic events. We tried to identify the clinical characteristics and risk factors of thrombotic events in a large sample-size retrospective cohort and investigate the causal relationship by Mendelian randomization (MR) analysis. Method In this retrospective, observational study, all hospitalized AAV patients were included in a single-center tertiary hospital in China from Jan 2013 to April 2022. Clinical data were collected for multivariate regression analysis to determine the risk factors of thrombotic events. As for MR analysis, we selected single nucleotide polymorphisms (SNPs) related to AAV from published genome-wide association studies. The outcome data containing deep vein thrombosis (DVT) and pulmonary embolism (PE) were extracted from the UK biobank. The inverse variance weighted (IVW) method and weighted median (WM) were performed in MR analysis. Results A total of 1203 primary AAV patients were enrolled, with 11.3% developing thrombotic events, with the average age of 49 (ranging from 43.75 to 59.75), and males occupied 56.3%. AAV patients with thrombosis were older (>65 years, 44.9% vs. 29.9%, P<0.001) and with more commodities like chronic kidney disease (CKD, 22.8%)or artery disease(CAD, 11.8%). The thrombotic incidences were more common in eosinophilic granulomatosis with polyangiitis (EGPA, 19.5%), with prolonged hospitalization without significant difference in hospital mortality. Multivariate regression suggested that age over 65 years (OR = 1.574, P = 0.029), EGPA (OR = 3.686, P = 0.029), elevated D-dimer (>2 mg/L, OR = 7.119, P<0.001), and end-stage renal disease (ESRD) status were associated with thrombosis events in patients with AAV. In addition, MR analysis showed that EGPA could increase the risk of developing DVT and PE (OR = 1.0038, 95%CI = 1.0035-1.0041, P = 0.009). Conclusion Thrombotic events were not rare in Chinese patients with AAV with independent risk factors such as highly elevated D-dimer and EGPA, which served as a causal risk factor for DVT and PE.